Different concentrations of various radiopharmaceuticals in the two main liver lobes: a preliminary study in clinical patients

Background At clinical scintigraphic examinations of the abdomen using single photon emission computed tomography (SPECT), we have observed a different distribution between the left and right main liver lobes of various radiopharmaceuticals. This was studied retrospectively in clinical patients.Methods Examinations with [¹²³I]-metaiodobenzylguanidine MIBG; (n = 19), a ^99mTc-labelled monoclonal antibody against granulocytes (n = 18), and ¹¹¹In-pentetreotide (n = 26) were assessed. There was no known history of, or risk factor for liver disease, and all lobes showed a uniform activity distribution. Twenty healthy volunteers underwent consecutive examinations with ^99mTc-dimethyliminodiacetic acid (HIDA). The activity ratios between the left and right main liver lobes were calculated from the transverse tomographic (SPECT) sections.Results The left : right lobar activity ratio for [¹²³I]-MIBG was (mean ± SD) 1.25 ± 0.21 (null hypothesis = 1.00; P < 0.001); for the antibody, acquisition after 3–5 h was 0.98 ± 0.06 (NS) and after 20–24 h, 0.99 ± 0.11 (NS); for ¹¹¹In-pentetreotide, 0.90 ± 0.09 (P < 0.001); for ^99mTc-HIDA, immediate acquisition, 0.68 ± 0.12 (P < 0.001) and acquisition at 7 min, 0.66 ± 0.12 (P < 0.001).Conclusions The differences in tracer uptake between the liver lobes cannot be caused only by differences in blood flow. One explanation of the higher uptake of [¹²³I]-MIBG by the left lobe may be a greater presence of catecholamines and a higher sympathetic nerve density in this liver portion. Consequently, there may be a functional difference between the two main liver lobes.     

A comparison of the in vivo biochemical responses to exogenous parathyroid hormone-(1-34) [PTH-(1-34)] and PTH-related peptide-(1-34) in man.

PTH-related peptide (PTHrP) is one of the etiological factors associated with hypercalcemia of malignancy in humans and rodents. In both in vivo and in vitro animal systems its actions mimic those of PTH; however, its bioactivity in humans has not previously been assessed. Therefore, we compared the actions of the synthetic human (h) analogs hPTHrP-(1-34) and hPTH-(1-34) when given by iv infusion to 15 healthy subjects, aged 25 +/- 3 yr. Three 12-h test infusions were given to each subject in the order: hPTH-(1-34) at a dose of 8 pmol/kg.h, an equimolar dose (8 pmol/kg.h) of PTHrP-(1-34) (low dose), and a 10-fold higher dose (80 pmol/kg.h) of hPTHrP-(1-34) (high dose). PTH infusion resulted in significant increases from basal values in serum total ionized calcium, urinary phosphate and cAMP, and serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2d3]. No significant increases from basal values in any of these variables were observed during low dose PTHrP infusion. However, a 10-fold higher dose of PTHrP significantly increased serum calcium from 2.36 +/- 0.07 to 2.63 +/- 0.16 mmol/L (P less than 0.003), ionized calcium from 1.22 +/- 0.03 to 1.39 +/- 0.09 mmol/L (P less than 0.003), urinary phosphate from 0.21 +/- 0.19 to 0.31 +/- 0.16 mmol/L glomerular filtrate (P less than 0.05), urinary cAMP from 37 +/- 18 to 53 +/- 28 nmol/L glomerular filtrate (P less than 0.01), and serum 1,25-(OH)2D3 from 29.8 +/- 12.1 to 46.0 +/- 20.3 pmol/L (P less than 0.01). For each variable these changes were statistically equivalent to the increases observed during PTH infusion. The molar concentrations of circulating immunoreactive PTH-(1-34) and PTHrP-(1-34) (at the higher dose) achieved during infusion were at a ratio of 1:3. These results suggest that the in vivo actions of synthetic hPTHrP-(1-34) are comparable to those of hPTH-(1-34), but its biological activity after infusion may be less than that of hPTH-(1-34). Moreover, the increased concentrations of serum 1,25-(OH)2D3 observed with administration of hPTHrP-(1-34) are unlike the changes seen in hypercalcemia of malignancy in which levels of this vitamin D metabolite are frequently depressed.     

The relative accuracies of ECG precordial lead waveforms derived from EASI leads and those acquired from paramedic applied standard leads

Accurate precordial electrode placement can be difficult in emergency situations leading either to loss of time or diminished accuracy. A possible solution is the quasi-orthogonal EASI lead system, with only five electrodes and easily defined landmarks to provide a derived 12-lead electrocardiogram (ECG). The purpose of this study was to test the hypothesis that precordial waveforms in EASI-derived ECGs have no greater deviation from those in gold standard ECGs, than do the precordial waveforms in paramedic acquired standard ECGs. Twenty paramedics applied the standard precordial electrodes employing the routine procedure. A certified ECG technician applied the 6 standard precordial electrodes in their correct gold standard positions, and the EASI electrodes. 12-lead ECGs were obtained from the paramedics' standard leads, and derived from the EASI leads, for comparison with the gold standard ECG. In each precordial lead recording, 6 computer-measured QRS-T waveform parameters were considered. Differences between deltaEASI-gold standard versus deltaparamedic-gold standard were calculated for every waveform in every lead resulting in 720 comparisons. EASI and paramedic results were "equally accurate" in 47%, the paramedic was more accurate in 31%, and EASI was more accurate in the remaining 22%. The differences from gold standard recording of precordial waveforms in ECGs derived from the EASI leads and those acquired via paramedic-applied standard electrodes are similar. The results suggest that the EASI lead system may provide an alternative to the standard ECG precordial leads to facilitate data acquisition and possibly save valuable time in emergency situations.     

Regulation of Keratinocyte Growth Factor (KGF) and KGF Receptor mRNAs by Nutrient Intake and KGF Administration in Rat Intestine

The aim of this study was to investigate the regulation of keratinocyte growth factor (KGF) and KGF receptor mRNAs by diet and KGF treatment in rat intestine. Fasting for three days up-regulated KGF and KGF receptor mRNA levels in ileum and increased KGF receptor mRNA expression in colon. KGF and KGF receptor mRNA levels returned toward control values with ad libitum refeeding but remained elevated when refeeding was limited to 25% of ad libitum intake. KGF treatment during nutrient repletion did not alter intestinal KGF mRNA levels but increased KGF receptor mRNA abundance in ileum and colon. We conclude that the increase in KGF and KGF receptor mRNAs induced by malnutrition may be an adaptive response to attenuate gut mucosal atrophy in this setting. The gut-trophic effects of KGF treatment may be mediated, in part, by up-regulation of the KGF receptor mRNA in small bowel and colon.     

Depression and anxiety in adults with congenital heart disease: a pilot study

OBJECTIVE: To examine the presence of depression and anxiety in adults with congenital heart disease and the association of medical severity with depression and anxiety. DESIGN: Prospective, pilot study. SETTING: An adult outpatient cardiology clinic in university-affiliated children's hospital in Northeast. PATIENTS: Twenty-two adult patients with congenital heart disease followed in an adult cardiology clinic. Patients were selected who had no evidence of emotional or behavioral difficulties, (ie, no symptoms of depression or anxiety). Outcome Measures Standardized semi-structured psychiatric interview with structured checklist eliciting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criteria for depressive and anxiety disorders, Brief Symptom Inventory (BSI), and the Cardiologist's Perception of Medical Severity scale. RESULTS: Among patients who had been assumed to be "well adjusted," 36.4% were experiencing a diagnosable psychiatric disorder, with anxiety or depressive symptoms being prominent. There were 6 patients (27.3%) who had BSI scores above 63 indicating pathological emotional functioning. There was significant convergent validity between the clinical diagnoses of depression and anxiety using both diagnostic interviews to identify DSM-IV diagnostic conditions and the BSI. There were significant associations between patient's medical severity scores and with the DSM-IV diagnosis of depression and the BSI global index score and depression subscale. CONCLUSIONS: This pilot study raises important concerns about the emotional functioning of many adults facing congenital heart disease, particularly those with complex lesions. From a clinical perspective, this work suggests that health care professionals should be alert for emotional difficulties and the possible need for psychological intervention for adult survivors of congenital heart disease even among those that are seemingly emotionally well adjusted.     

Safety, efficacy, and pharmacokinetics of adefovir dipivoxil in children and adolescents (age 2 to <18 years) with chronic hepatitis B

This study investigated the efficacy, safety, and pharmacokinetics of adefovir dipivoxil (ADV) in children and adolescents with chronic hepatitis B (CHB). A total of 173 treatment-naive and treatment-experienced children with hepatitis B e antigen (HBeAg)+ CHB were randomized to ADV or placebo. Randomization was stratified by age (2 to <7 years; >7 to <12 years; >12 to <18 years) and prior treatment. Significantly more ADV-treated subjects aged 12 to <18 years achieved the primary efficacy endpoint (serum hepatitis B virus [HBV] DNA <1,000 copies/mL and normal alanine aminotransferase) compared to placebo-treated subjects (23% versus 0%; P = 0.007). In the younger groups, differences between ADV and placebo at the end of blinded treatment were not statistically significant. More ADV-treated subjects had HBeAg seroconversion: 18 of 113 (15.9%) versus three of 57 (5.3%) (but P = 0.051), and more met the combined endpoint of HBeAg seroconversion, HBV DNA <1,000 copies/mL and normal alanine aminotransferase (12/113 versus 0/57; P = 0.009). No subject developed an ADV-associated mutation that has been linked to HBV DNA rebound (that is, mutations rtN236T or rtA181V). ADV plasma concentrations were comparable across groups and within the target range. ADV treatment was well tolerated; no new safety issues were identified. Treatment-related adverse events were reported for 12% of ADV-treated and 10% of placebo-treated subjects. After 48 weeks of ADV treatment, antiviral efficacy in subjects ages 12 to <18 years with HBeAg+ CHB was similar to that observed in a study in adult treatment-naive subjects with HBeAg+ CHB. ADV was not different from placebo in subjects aged 2 to 11 years despite adequate plasma ADV exposure in all three age groups. CONCLUSION: ADV showed significant antiviral efficacy in subjects aged 12 to 17 years with HBeAg+ CHB, but was not different from placebo in subjects aged 2 to 11 years.     

Panhypopituitarism associated with severe retroperitoneal fibrosis

A 43-year-old man, with a history of central diabetes insipidus diagnosed 3 years previously, complained about reduced libido. An MRI scan showed a suprasellar lesion just below the supraoptic recess of the third ventricle. A stereotactically guided biopsy revealed fibrous glia, but no other specific tissue and no inflammatory cells. Two months later the patient presented with fatigue and muscular weakness. Tertiary adrenal failure and hypothyroidism were diagnosed by endocrine function tests and therapy with levothyroxine and hydrocortisone was started. Another 2 months later the patient was admitted with giddiness, nausea, peripheral oedema and oliguria. Radiological imaging and an open transperitoneal kidney exploration showed severe fibrosis around both ureters. Histological examination confirmed the diagnosis of idiopathic retroperitoneal fibrosis. Presumably the suprasellar tumour was the first manifestation of retroperitoneal fibrosis. Once the diagnosis 'idiopathic retroperitoneal fibrosis' is confirmed, fibrotic manifestations and complications involving extra-retroperitoneal tissues including the endocrine system, should be sought.     

Nifedipine and Cancer Mortality: Ten-Year Follow-up of 2607 Patients After Acute Myocardial Infarction

Recent publications contended that the use of short-acting calcium antagonists may double the risk of cancer incidence and possibly increase mortality in hypertensive patients. The purpose of this study was to assess the risk ratio for cancer mortality associated with nifedipine in a large population of patients post–myocardial infarction. Cancer mortality data, over a 10-year period, were obtained on 2607 hospital survivors of acute myocardial infarction who were screened, but not included, in the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT I) study. In this group of patients, 526 (20%) were on nifedipine, according to their treating physicians decision. In the cohort of screened patients not included in SPRINT I, there were 22 (4.2%) cancer-related deaths in the patients on nifedipine compared with 114 (5.5%) in the group not treated with nifedipine (P= 0.23). In multivariate analysis, the 10-year cancer mortality risk ratio associated with nifedipine therapy was 1.06 (95% Cl 0.52–2.18). The current analysis shows no evidence of an increased risk of cancer mortality in a large number of patients treated at baseline with nifedipine.